Document Detail

Cisplatin-induced apoptosis involves a Fas-ROCK-ezrin-dependent actin remodelling in human colon cancer cells.
MedLine Citation:
PMID:  20202822     Owner:  NLM     Status:  MEDLINE    
In human colon cancer cells, cisplatin-induced apoptosis involves the Fas death receptor pathway independent of Fas ligand. The present study explores the role of ezrin and actin cytoskeleton in relation with Fas receptor in this cell death pathway. In response to cisplatin treatment, a rapid and transient actin reorganisation is observed at the cell membrane by fluorescence microscopy after Phalloidin-FITC staining. This event is dependent on the membrane fluidification studied by electron paramagnetic resonance and necessary for apoptosis induction. Moreover, early after the onset of cisplatin treatment, ezrin co-localised with Fas at the cell membrane was visualised by membrane microscopy and was redistributed with Fas, FADD and procaspase-8 into membrane lipid rafts as shown on Western blots. In fact, cisplatin exposure results in an early small GTPase RhoA activation demonstrated by RhoA-GTP pull down, Rho kinase (ROCK)-dependent ezrin phosphorylation and actin microfilaments remodelling. Pretreatment with latrunculin A, an inhibitor of actin polymerisation, or specific extinction of ezrin or ROCK by RNA interference prevents both cisplatin-induced actin reorganisation and apoptosis. Interestingly, specific extinction of Fas receptor by RNA interference abrogates cisplatin-induced ROCK-dependent ezrin phosphorylation, actin reorganisation and apoptosis suggesting that Fas is a key regulator of cisplatin-induced actin remodelling and is indispensable for apoptosis. Thus, these findings show for the first time that phosphorylation of ezrin by ROCK via Fas receptor is involved in the early steps of cisplatin-induced apoptosis.
Amélie Rebillard; Sandrine Jouan-Lanhouet; Elodie Jouan; Patrick Legembre; Mathieu Pizon; Odile Sergent; David Gilot; Xavier Tekpli; Dominique Lagadic-Gossmann; Marie-Thérèse Dimanche-Boitrel
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-04
Journal Detail:
Title:  European journal of cancer (Oxford, England : 1990)     Volume:  46     ISSN:  1879-0852     ISO Abbreviation:  Eur. J. Cancer     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-03     Completed Date:  2010-09-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9005373     Medline TA:  Eur J Cancer     Country:  England    
Other Details:
Languages:  eng     Pagination:  1445-55     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Ltd. All rights reserved.
EA 4427 SeRAIC, Faculty of Pharmacy, University of Rennes 1, IFR 140 GFAS, Rennes F-35043, France.
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MeSH Terms
Antigens, CD95 / drug effects*,  metabolism
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects,  physiology
Cisplatin / pharmacology*
Colonic Neoplasms / drug therapy,  metabolism*,  pathology
Cytoskeletal Proteins / drug effects*,  metabolism
Fas Ligand Protein / drug effects,  metabolism
Protein-Serine-Threonine Kinases / drug effects,  metabolism*
Signal Transduction / drug effects
Tumor Cells, Cultured
Reg. No./Substance:
0/Antigens, CD95; 0/Antineoplastic Agents; 0/Cytoskeletal Proteins; 0/Fas Ligand Protein; 0/ezrin; 15663-27-1/Cisplatin; EC 2.7.1.-/actin kinase; EC Kinases

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